Montelukast sodium (USP Dictionary of USAN and International Drug Names, 1990) has structural formula IV: ##STR3##
It is a leukotriene antagonist useful in the treatment of asthma and related problems. Its synthesis is fully described in European Patent publication 0 480,717. An important intermediate in the synthesis of montelukast sodium is the monoaldehyde of Structure III shown above. A process for the preparation of this monoaldehyde is described in U.S. Pat. No. 4,851,409 by Young et al. During the development of the overall process for the manufacture of montelukast sodium a much improved process for the monoaldehyde step was developed resulting in a yield of about 65% and a consumption of about 1.5 equivalents of isophthalaldehyde per equivalent of 7-chloroquinaldine.
Now with the present invention there is provided a process whereby the yield of monoaldehyde is increased from 65% to about 82% and the rate of consumption of isophthalaldehyde is reduced from about 1.5 equivalents to about 1.2 equivalents per equivalent of 7-chloroquinaldine.